The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection.
Natural products with interesting biological properties and structural diversity have often served as valuable lead drug candidates for the treatment of human diseases. Salacinol, a naturally occurring alpha-glucosidase inhibitor, was shown to be one of the active principles of the aqueous extract of a medicinal plant that has been prescribed traditionally as an Ayurvedic treatment for type II diabetes. Salacinol contains an intriguing zwitterionic sulfonium-sulfate structure that comprises a 1,4-anhydro-4-thio-D-arabinitol core and a polyhydroxylated acyclic chain.
BACKGROUND: Articular cartilage from patients with osteoarthritis is characterized by a decreased concentration and reduced size of glycosaminoglycans. Degeneration of the cartilage matrix is a multifactorial process, which is due in part to accelerated glycosaminoglycan catabolism. Recently, we have demonstrated that hexosaminidase represents the dominant glycosaminoglycan-degrading glycosidase released by chondrocytes into the extracellular compartment and is the dominant glycosidase in synovial fluid from patients with osteoarthritis.
Drug Metabolism and Disposition: The Biological Fate of Chemicals
CYP2E1 is widely accepted as the sole form of cytochrome P450 responsible for alcohol-mediated increases in acetaminophen (APAP) hepatotoxicity. However, we previously found that alcohol [ethanol and isopentanol (EIP)] causes increases in APAP hepatotoxicity in Cyp2e1(-/-) mice, indicating that CYP2E1 is not essential. Here, using wild-type and Cyp2e1(-/-) mice, we investigated the relative roles of CYP2E1 and CYP3A in EIP-mediated increases in APAP hepatotoxicity.